Human p68 kinase exhibits growth suppression in yeast and homology to the translational regulator GCN2

K. L. Chong, L. Feng, K. Schappert, E. Meurs, T. F. Donahue, J. D. Friesen, A. G. Hovanessian, B. R.G. Williams

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Abstract

The human p68 kinase is an interferon-regulated enzyme that inhibits protein synthesis when activated by double-stranded RNA. We show here that when expressed in Saccharomyces cerevisiae, the p68 kinase produced a growth suppressing phenotype resulting from an inhibition of polypeptide chain initiation consistent with functional protein kinase activity. This slow growth phenotype was reverted in yeast by two different mechanisms: expression of the p68 kinase N-terminus, shown to bind double-stranded RNA in vitro and expression of a mutant form of the α-subunit of yeast initiation factor 2, altered at a single phosphorylatable site. These results provide the first direct in vivo evidence that the p68 kinase interacts with the α-subunit of eukaryotic initiation factor 2. Sequence similarity with a yeast translational regulator, GCN2, further suggests that this enzyme may be a functional homolog in higher eukaryotes, where its normal function is to regulate protein synthesis through initiation factor 2 phosphorylation.

Original languageEnglish
Pages (from-to)1553-1562
Number of pages10
JournalThe EMBO Journal
Volume11
Issue number4
Publication statusPublished - 1 Jan 1992
Externally publishedYes

Keywords

  • dsRNA
  • eIF-2α phosphorylation
  • GCN2
  • Growth inhibition
  • p68 Kinase

Cite this

Chong, K. L., Feng, L., Schappert, K., Meurs, E., Donahue, T. F., Friesen, J. D., Hovanessian, A. G., & Williams, B. R. G. (1992). Human p68 kinase exhibits growth suppression in yeast and homology to the translational regulator GCN2. The EMBO Journal, 11(4), 1553-1562.